The objective of the proposed research is to identify the sequential stages of tissue and cellular events which occur during the induction of renal neoplasia by nitroso compounds and to develop further cell culture models which will provide information that will correlate directly with the in vivo process. Emphasis will be placed on the identification of target cells and their responses to carcinogens, and on the identification of precursor lesions and their progression, utilizing techniques of isotopic labeling and electron microscopy. Cell cultures derived from carcinogen-treated animals will provide simpler experimental systems facilitating the analysis of target cells in terms of their ultrastructural, proliferative, biochemical and functional characteristics and of the stages in the transformation process. Additionally, it is proposed to seek and test for modifying factors effective in the tumor systems and to investigate their mode of action in the pre-determined stages of renal tumor induction. The broad objectives of the project are to further the understanding of the basic biology of human renal neoplasia and of the process of chemical carcinogenesis in general, and to identify strategies which may reverse or inhibit the cancer process.